Our long-term goal is to understand how the signal transduction cascade that comprises the phototransduction process is organized and controlled, and how the photoreceptive organelle is assembled and maintained. This application focuses on the biogenesis of the specialized photoreceptive organelle that houses and organizes the phototransduction machinery of Drosophila melanogaster. Our specific aims are: 1. Characterize the biology of rhabdomere biogenesis in wild type flies, and identify molecular markers for the specific stages of initiation and elaboration of rhabdomeres. 2. Develop a comprehensive genetic screen to isolate mutants with defects in rhabdomere initiation and elaboration. 3. Define the basis of the rhabdomeric defect in the various mutants by characterizing them genetically, cell biologically and physiologically. Use genetic epistasis to localize the site of action of the defective genes. 4. Isolate the defective genes and identify the nature of the change. Introduce the wild-type and/or defective gene back into flies by P-element mediated germ line transformation and test for rescuing and/or induction of retinal dysfunction (i.e. dominant phenotypes). 5. Use the Drosophila genes to isolate the corresponding human homologs. Make those sequences available to the community working on vertebrate models and attempt to rescue the Drosophila mutants (or generate dominant mutants) with the human counterparts.